Diepoxybutane cytotoxicity on mouse germ cells is enhanced by in vivo glutathione depletion: a flow cytometric approach.
Diepoxybutane is one of the key metabolites of butadiene, a compound of high environmental and occupational concern. The effects of diepoxybutane on mouse reproductive cells have been previously characterized by flow cytometry demonstrating a specific, dose-dependent cytotoxicity for differentiating spermatogonia. It is known that butadiene epoxides, deriving from butadiene bioactivation by cytochrome P450-monooxygenase systems, can be enzymatically conjugated to glutathione by glutathione S-transferases. In this paper, we tested the hypothesis whether a pretreatment with phorone, a well-known intracellular glutathione depleter, would enhance the germ cell cytotoxicity of diepoxybutane. Results were consistent with an active role played in vivo by the glutathione-detoxifying system, as diepoxybutane cytotoxicity was increased after chemically induced reduction of glutathione concentration.
Spanò
M
M
Section of Toxicology and Biomedical Sciences, ENEA Casaccia, Rome, Italy. spanomrc@casaccia.enea.it
Cordelli
E
E
Leter
G
G
Pacchierotti
F
F
D000818:Animals; D002070:Butadienes / Q000378:metabolism / Q000633:toxicity; D002453:Cell Cycle / Q000502:physiology; D004247:DNA / Q000032:analysis; D004787:Environmental Pollution; D004852:Epoxy Compounds / Q000633:toxicity*; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D005854:Germ Cells / Q000187:drug effects*; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000172:deficiency*; D007211:Indoles / Q000378:metabolism; D007659:Ketones / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D011003:Ploidies; D013087:Spermatids / Q000187:drug effects
D002070:Butadienes; D004852:Epoxy Compounds; D005456:Fluorescent Dyes; D007211:Indoles; D007659:Ketones; D009153:Mutagens; C007293:DAPI; C007366:diepoxybutane; C018637:phorone; D004247:DNA; D005978:Glutathione; C031763:1,3-butadiene